Histone deacetylase inhibitor-mediated cell death is distinct from its global effect on chromatin.

ABSTRACT: Romidepsin and vorinostat are histone deacetylase inhibitors (HDACis) that have activity in T-cell lymphomas, but have not gained traction in solid tumors. To gain deeper insight into mechanisms of HDACi efficacy, we systematically surveyed 19 cell lines with different molecular phenotypes, comparing romidepsin and vorinostat at equipotent doses. Acetylation at H3K9 and H4K8 along with 22 other histone lysine acetylation and methylation modifications were measured by reverse phase proteomics array (RPPA), and compared with growth inhibition (IC50), and cell cycle arrest. These assays typically used to assess HDACi effect showed that acetylation and methylation of specific lysine residues in response to HDACis were consistent across cell lines, and not related to drug sensitivity. Using a t

SUBMITTER: Luchenko VL 

PROVIDER: S-EPMC4646083 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature